The 2-deoxyglucose (2-DG) technique was used to investigate general and localized changes in metabolic activity within the brains of animals exposed to drugs capable of producing dependence. We studied the acute effects (one dose), chronic effects (after a period of administration sufficient to produce physical dependence), and the effects during withdrawal from the drug under study. Specifically, we looked at the effects of ethanol, phenobarbital, and diazepam (Valium). Withdrawal from ethanol, phenobarbital, and diazepam produced several similarities. Among the similarities noted were a generalized increase in 2-DG uptake, 400 micrometer wide columns of increased uptake in the sensorimotor cortex, and ovoid areas of increased uptake in the cerebellum. Differences were noted between the phenobarbital and ethanol withdrawal autoradiographs. One striking example was that the lateral geniculate showed a localized increase in uptake in the dorsal portion during phenobarbital but not ethanol withdrawal. Further analysis is needed for comparisons with diazepam withdrawals. When diazepam is given to an animal withdrawing from ethanol, the prominent sensorimotor cortical columns and ovoid areas of increased uptake in the cerebellum seen in the ethanol withdrawing rat were not observed. The acute studies of ethanol administration indicates that at low doses (0.8 g/kg), ethanol may increase, moderate doses (1.6 g/kg) appear to decrease, and high doses (3.2 g/kg) show a mixed response with respect to 2-deoxyglucose uptake. Acute phenobarbital appears to decrease uptake while diazepam given acutely appears to have no effect on uptake. Further analysis is needed to clarify the results from the acute phenobarbital, withdrawing diazepam, acute diazepam, and the administration of diazepam to ethanol withdrawing rats.